A substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication recognized or defined by the U.S. Food, Drug, and Cosmetic Act. A substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication recognized or defined by the U.S. Food, Drug, and Cosmetic Act. A drug is any chemical or biological substance, synthetic or non-synthetic A drug is any chemical or biological substance, synthetic or non-synthetic DRUG

A drug is anything that affects the way an organism works. A drug is anything that affects the way an organism works. Drugs can be taken to enhance function, such as a student drinking caffeine to enhance alertness. Drugs can be taken to enhance function, such as a student drinking caffeine to enhance alertness. For now we only consider drugs which are used to cure a disease. For now we only consider drugs which are used to cure a disease.

A disease is often thought of as an infection, where a bacteria, virus, or other living thing invades the body. A disease is often thought of as an infection, where a bacteria, virus, or other living thing invades the body. However, a disease is anything which affects the proper functioning of the body. However, a disease is anything which affects the proper functioning of the body. It can be an infection, a genetic disorder, or the result of environmental conditions such as malnourishment, poisoning, or stress. It can be an infection, a genetic disorder, or the result of environmental conditions such as malnourishment, poisoning, or stress.

You may find it easy to think of the body as a factory. You may find it easy to think of the body as a factory. Individual organs can be seen as machinery. The actual nuts, bolts, screwdrivers, and wrenches that make up all the machinery are the equivalent of proteins, little chunks of organic material that move things around in the body and attach them together. Individual organs can be seen as machinery. The actual nuts, bolts, screwdrivers, and wrenches that make up all the machinery are the equivalent of proteins, little chunks of organic material that move things around in the body and attach them together. Most of the work in our body is done by PROTEINS (tiny molecular machines!) Most of the work in our body is done by PROTEINS (tiny molecular machines!) Continued

The body contains thousands of different kinds of proteins. The body contains thousands of different kinds of proteins. The construction of each is determined by the DNA in the nucleus of each cell. The construction of each is determined by the DNA in the nucleus of each cell. DNA may be thought of as long strings of instructions which code for how each protein is too be built. DNA may be thought of as long strings of instructions which code for how each protein is too be built.

How Pharmaceutical Drugs are Made 1. Initial Concept 2. Research & Development 3. Clinical Trials 4. FDA Approval 5. Marketing

Dept. of Pharmaceutics 709/07/2007 INITIAL CONCEPT

Initial Concept The drug company will decide which disease to target The drug company will decide which disease to target Research will be done to find the biological target for the drug’s action (usually a PROTEIN) Research will be done to find the biological target for the drug’s action (usually a PROTEIN)

Initial Concept Many drugs are small synthetic molecules that bind to the active site of a protein Many drugs are small synthetic molecules that bind to the active site of a protein So, the first step is identifying the protein to target So, the first step is identifying the protein to target

Dept. of Pharmaceutics 1009/07/2007 RESEARCH & DEVELOPMENT

Once a company decides on a disease and target protein, its next step will be to make a library of chemical compounds (potential drugs) to test on the protein. Once a company decides on a disease and target protein, its next step will be to make a library of chemical compounds (potential drugs) to test on the protein. Literally hundreds and sometimes thousands of chemical compounds must be made and tested in an effort to find one that can achieve a desirable result. Literally hundreds and sometimes thousands of chemical compounds must be made and tested in an effort to find one that can achieve a desirable result. Computers can be used to simulate a chemical compound and design chemical structures that might work against it. Computers can be used to simulate a chemical compound and design chemical structures that might work against it. Synthesis and Purification

In Vitro (outside of a living organism) testing is performed on purified proteins and well as cultured cell lines In Vitro (outside of a living organism) testing is performed on purified proteins and well as cultured cell lines In Vivo (within a living organism) testing is performed on living animals. Rodents are typically used for animal testing. In Vivo (within a living organism) testing is performed on living animals. Rodents are typically used for animal testing. Pre-clinical Drug Development

Drug companies make every effort to use as few animals as possible and to ensure their humane and proper care. Drug companies make every effort to use as few animals as possible and to ensure their humane and proper care. Animal testing is used to measure how much of a drug is absorbed into the blood, how it is broken down chemically in the body, the toxicity of the drug and its breakdown products metabolites, and how quickly the drug and its metabolites are excreted from the body Animal testing is used to measure how much of a drug is absorbed into the blood, how it is broken down chemically in the body, the toxicity of the drug and its breakdown products metabolites, and how quickly the drug and its metabolites are excreted from the body The Three Rs of Animal Use in Research The Three Rs of Animal Use in Research RESPECT for the animal REDUCE the number of animals used REUSE animals for multiple studies if possible Animal Testing

Dept. of Pharmaceutics 1409/07/2007 CLINICAL TRIALS

Phase 1 Clinical Studies Phase 1 includes the initial introduction of an investigational new drug into human. Phase 1 includes the initial introduction of an investigational new drug into human. Phase 1 studies usually conducted in healthy volunteer. Phase 1 studies usually conducted in healthy volunteer. (Exceptions may include toxic drugs such as chemotherapies) Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. The total number of subjects included in Phase I studies varies with the drug, but is generally in the range of 20 to 80 The total number of subjects included in Phase I studies varies with the drug, but is generally in the range of 20 to 80 Phase 1 studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and if possible to gain early evidence on effectiveness. Phase 1 studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and if possible to gain early evidence on effectiveness.

Phase 2 Clinical Studies The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety. The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety. Phase 2 includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness of the drug for a particular indication or indications in patients with the disease or condition. Phase 2 includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness of the drug for a particular indication or indications in patients with the disease or condition. This phase of testing also helps determine the common short-term side effects and risks associated with the drug. This phase of testing also helps determine the common short-term side effects and risks associated with the drug. Phase 2 studies are typically well-controlled, closely monitored, and conducted in a relatively small number of patients usually involving several hundred people. Phase 2 studies are typically well-controlled, closely monitored, and conducted in a relatively small number of patients usually involving several hundred people.

The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Phase 3 studies usually include several hundred to several thousand people. Phase 3 studies usually include several hundred to several thousand people. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in Phase 2 and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in Phase 2 and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug. Phase 3 studies also provide an adequate basis for extrapolating the results to the general population and transmitting that information in the physician labeling. Phase 3 studies also provide an adequate basis for extrapolating the results to the general population and transmitting that information in the physician labeling. Phase 3 Clinical Studies

Dept. of Pharmaceutics 1809/07/2007 FDA APPROVAL

FDA Approval… hopefully! A NDA (New Drug Application is submitted to the FDA (Food & Drug Administration) A NDA (New Drug Application is submitted to the FDA (Food & Drug Administration) Is the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks. Is the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks. Is the drug's proposed labeling (package insert) is appropriate, and what it should contain. Is the drug's proposed labeling (package insert) is appropriate, and what it should contain. Are the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity. Are the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.

Dept. of Pharmaceutics 2009/07/2007 MARKET

Drug Goes to Market Drug is sold to the general public and medical community Drug is sold to the general public and medical community Advertisements $$ Advertisements $$ Education of health care workers, especially prescribing physicians on the usefulness of the new drug Education of health care workers, especially prescribing physicians on the usefulness of the new drug

Phase IV Clinical Studies  Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.  If you have ever taken a drug, you have been a study participant in phase IV clinical trials!